Development and evaluation of a loop-mediated isothermal amplification method for rapid diagnosis of Bordetella pertussis infection

We developed a loop-mediated isothermal amplification (LAMP) method to detect Bordetella pertussis infection. This LAMP assay detected B. pertussis with high sensitivity, but not other Bordetella species. Among nasopharyngeal swab samples from subjects with suspected pertussis, LAMP results showed a high level of agreement with results of conventional PCR. This method is a rapid, sensitive, and specific method for diagnosis of B. pertussis infection even in clinical laboratories with no specific equipment.     

Rifaximin in non‐alcoholic steatohepatitis: An open‐label pilot study

Aim

Gut microbial dysbiosis is implicated in the pathogenesis of non‐alcoholic steatohepatitis (NASH). We investigated downstream effects of gut microbiota modulation on markers of hepatic inflammation, steatosis, and hepatic and peripheral insulin sensitivity in patients with NASH using rifaximin therapy.

Methods

Patients with biopsy‐proven NASH and elevated aminotransferase values were included in this open‐label pilot study, all receiving 6 weeks rifaximin 400 mg twice daily, followed by a 6‐week observation period. The primary endpoint was change in alanine aminotransferase (ALT) after 6 weeks of rifaximin. Secondary endpoints were change in hepatic lipid content and insulin sensitivity measured with a hyperinsulinemic–euglycemic clamp.

Results

Fifteen patients (13 men and 2 women) with a median (range) age of 46 (32–63) years were included. Seven had diabetes on oral hypoglycemic medications and 8 had no diabetes. After 6 weeks of therapy, no differences were seen in ALT (55 [33–191] vs. 63 [41–218] IU/L, P = 0.41), peripheral glucose uptake (28.9 [19.4–48.3] to 25.5 [17.7–47.9] μmol/kg/min, P = 0.30), hepatic insulin sensitivity (35.2 [15.3–51.7]% vs. 30.0 [10.8–50.5]%, P = 0.47), or hepatic lipid content (21.6 [2.2–46.2]% vs. 24.8 [1.7–59.3]%, P = 0.59) before and after rifaximin treatment. After 12 weeks from baseline, serum ALT increased to 83 (30–217) IU/L, P = 0.02. There was a significant increase in the homeostasis model assessment–estimated insulin resistance index (P = 0.05). The urinary metabolic profile indicated a significant reduction in urinary hippurate with treatment, which reverted to baseline after cessation of rifaximin, although there was no consistent difference in relative abundance of fecal microbiota with treatment.

Conclusion

These data do not indicate a beneficial effect of rifaximin in patients with NASH.     

Inhibitors of types I and II dehydroquinase

Inhibitors of varying potency have been developed for types I and II 3-dehydroquinate dehydratase (dehydroquinase), enzymes from the shikimate and quinate pathways that catalyse the dehydration of dehydroquinate to dehydroshikimate. These inhibitors have resulted from enzyme mechanistic studies and from the direct search for enzyme inhibitors with herbicidal, fungicidal or antimicrobial potential. This review discusses the design of the various inhibitors that have been produced so far and some structure-activity relationships. The majority of these inhibitors are based on dehydroquinate analogues, although some work has also been carried out on dehydroshikimate and bissulfonamides. Some discussion is also presented on advances in the synthesis of these types of compounds.     

The measurement of the depersonalisation-derealisation-syndrome with the German version of the Cambridge Depersonalisation Scale (CDS)

Self-rating scales have proved to be essential in the study of depersonalisation, which regrettably, is still seldom recognised in clinical practice. In recent studies the Cambridge Depersonalisation Scale (CDS) has emerged as an useful instrument for the study of depersonalisation. Here we report a validation study of the authorised German version of the CDS in a sample of 91 inpatients, 43 of whom had pathological depersonalisation and 48 without pathological depersonalisation. The SCID-D Interview for depersonalisation and derealisation was used as the gold standard and the German version of the Dissociative Experiences Scale was used to test the external validity of the scale. The German version of the CDS was found to have high internal consistency and reliability (alpha = 0,95 and Guttman Split-half = 0,95) and could differentiate patients with pathological depersonalisation from the control group. We therefore conclude that the German version of the CDS can be considered as reliable and valid.     

Effect of oral lipid administration on glucose homeostasis in small-for-gestational-age infants

The metabolic effect of feeding with 1.3 g/kg bw lipids (67% medium chain triglycerides) was studied in 15 small-for-gestational age (SGA) term infants. It was compared to a control group of 7 SGA term infants, to 7 term infants with an appropriate birth weight (AGA) and to 7 AGA preterm infants. Plasma glucose concentration rose from (M +/- SE) 3.6 +/- 0.2 to 4.4 +/- 0.3 mmol/l at 30 min in SGA term infants (p less than 0.01). A similar increase was observed in AGA term and preterm infants. The lipid load produced no change in plasma glucagon concentration but a significant increase in insulin/glucagon molar ratio was observed in AGA term infants only. In term SGA infants, the disappearance rate of glucose in plasma after the lipid load was similar to the control: 1.24% per min. The evolution of blood pyruvate and lactate concentration was not modified by the lipid load. Despite lower concentrations of free fatty acids and ketone bodies (KB) in SGA infants than in AGA term infants, the lipid load induced a 120% increase of ketone bodies in SGA infants and a 40% increase only in AGA infants. These data show that these lipids produce a hyperglycemic response in SGA infants as in AGA infants without any change of the disappearance rate of glucose. They suggest that these lipids can stimulate gluconeogenesis and ketogenesis in SGA infants.     

Course of the blood glucose level after cessation of a glucose infusion in the low-birth-weight infant

The evolution of plasma glucose concentration was investigated in 8 dysmature and 5 appropriate-for-gestational-age (AGA) preterm infants. Mean (+/- 1 SD) plasma glucose decreased from 3,3 +/- 0,8 to 2,3 +/- 1,2 mmol/l in 30 minutes (p less than 0,01) with two values below 1,8 mmol/l. It then increased to 2,7 +/- 0,7 mmol/l at 60 minutes with no values below 1,8 mmol. In 4 (AGA) preterm infants plasma glucose decreased from 2,73 +/- 0,76 to 2,04 +/- 1,6 mmol/l at 60 minutes. One preterm infant treated with theophylline showed an increase from 4,91 to 6,05 mmol/l at 60 minutes. A negative correlation was observed only in dysmature infants between the rate of glucose infusion and the maxima drop of plasma glucose (r = 0,77 ; p less than 0,01). In dysmature infants, a drop in plasma glucose appears in correlation to the previous infusion rate of glucose. However a counterregulation appears in all dysmature infants.     

Hyperammonemia in hypoglycemic preterm neonates

Plasma glucose, blood urea nitrogen, and ammonia were measured simultaneously in 44 newborns a few hours after birth. When the concentration of plasma glucose was below 30 mg/dl, plasma ammonia concentration was significantly higher (129 +/- 67 mumol/l) than in normoglycemic infants (74 +/- 33 mumol/l; p less than 0.01). Blood urea nitrogen was slightly lower in hypoglycemic infants (3.65 +/- 0.7 mmol/l) than in the control group (4.5 +/- 1 mmol/l) but the difference was not significant. These data show that hyperammonemia can be associated to hypoglycemia in low birth weight infants. Therefore, further investigations are required to determine the link between urea and glucose production rates in hypoglycemic newborns and whether hyperammonemia participates in the deleterious effects of hypoglycemia on the neonatal brain.     

Physikalische und physiologische Grundlagen des Rinneschen Versuches

Zusammenfassung Die Anwendung und diagnostische Bedeutung des Rinneschen Stimmgabelversuches stützt sich bisher auf rein empirische Erkenntnisse. In der vorliegenden Arbeit wird versucht, these durch exakte physikalische Untersuchungen zu überprüfen. Im einzelnen warden Messungen angestellt über das Schallfeld einer tönenden Stimmgabel in der Luft, die Abhängigkeit der Lautstarke von der Entfernung, die den Knochenschall beeinflussenden Bedingungen, insbesondere den Auflagedruck auf den Warzenfortsatz, die Dämpfung verschiedener Stimmgabeln, einmal bei Haltung wie zur Prüfung der Luftleitung, zum anderen beim Aufsetzen auf den Warzenfortsatz, die Differenz zwischen der Lautstärke des Luft- und Knochenschalles, den Einfluß von Störgerauschen auf den Ausfall des Rinneschen Versuches und die Bedeutung der Vibrationsschwelle. Aus den Untersuchungsergebnissen werden Folgerungen für die praktisch-klinische Anwendung des Stimmgabelversuches abgeleitet.

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Summary Clinical application and diagnostic evaluation of the Rinne test are based on purely empirical facts. The authors have undertaken to check these by exact physical examinations. Measurements were carried out concerning the sound field of a vibrating tuning fork, the loudness as a function of distance, the conditions influencing the bone-conduction, in particular the pressure against the mastoid bone, the decrement of different tuning forks when held for testing the air-conduction as opposed to the situation when it is placed on the mastoid, the ratio of loudness between airborne and bone-conducted sound, the influence of noise on the result of the Rinne test, and the role of the vibratory threshold. From the experimental facts conclusions are drawn for the clinical application of the Rinne test.

     

Serum gastrin level in early childhood.

Serum gastrin concentration was measured in newborns and infants with no gastrointestinal disorders, in the fasting state and after food stimulation. Mean fasting concentration in 14 newborns aged 1 to 12 days (130 . 4 pg/ml +/- 11 . 4 SE) was significantly higher than the mean value in 23 infants aged 1.5 to 22 months (101.4 +/- 6.6 pg/ml). Ingestion of the usual milk meal resulted in a definite rise of the serum gastrin level in the 5 subjects tested (3 newborns and 2 infants). The mean fasting serum gastrin level in 6 babies with hiatus hernia and gastro-oesophageal reflux was found to be no different from the corresponding value in 8 age-matched controls. However, a conspicuously raised fasting gastrin concentration was observed in one infant with lower oesophageal dyskinesia. The results indicate that the release of gastrin and the reactivity of the hormone-producing sites to food stimulation in early life are similar to those in adult humans. No defect of gastrin release was shown in patients with gastro-oesophageal reflux.